US3925381A - 6-Substituted 3-carbethoxyhydrazinopyridazine - Google Patents
6-Substituted 3-carbethoxyhydrazinopyridazine Download PDFInfo
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- US3925381A US3925381A US447523A US44752374A US3925381A US 3925381 A US3925381 A US 3925381A US 447523 A US447523 A US 447523A US 44752374 A US44752374 A US 44752374A US 3925381 A US3925381 A US 3925381A
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- Prior art keywords
- carbethoxyhydrazino
- pyridazine
- substituted
- mixture
- compounds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/20—Nitrogen atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Definitions
- R O NI-INHCOOC2H5 wherein R and R which may be the same or different, represent a lower alkyl group containing from I to 6 carbon atoms, an ally! group, a 2hydroxyethyl group or a 2-hydroxypropyl group, as well as the pharmaceutically acceptable salts thereof. Also a method of preparation. These compounds have antihypertensive activity.
- the present invention relates to new derivatives of pyridazine possessing remarkable pharmacodynamic properties. More particularly, the invention relates to new o-substituted 3'carbethoxyhydrazinopyridazines of the general formula: V
- the compounds of the invention and pharmaceutically acceptable salts thereof are useful as pharmaceuticals and are characterized by activity as antihypertensive agents.
- these compounds can be used in the form of conventional pharmaceutical preparations; for example, the aforesaid compounds can be mixed with conventional organic or inorganic, inert pharmaceutical carriers suitable for parenteral or enteral administration such as, for example, water, gelatin, lactose, starch, magnesium stearate, talc, vegetable oil, gums, polyalkylene glycols, vaseline or the like. They can be administered in conventional pharmaceutical forms, e.g. solid forms, for example, tablets, dragees, capsules and the like; or in liquid forms, for example, injectable solutions, suspensions or emulsions.
- conventional pharmaceutical forms e.g. solid forms, for example, tablets, dragees, capsules and the like
- injectable solutions, suspensions or emulsions for example, injectable solutions, suspensions or emulsions.
- compositions containing compounds of this invention can be subjected to conventional pharmaceutical expedients such as sterilisation and can contain conventional pharmaceutical excipients such as preservatives, stabilizing agents, wetting agents, emulsifying agents, salts for the adjustment of osmotic pressure or buffers.
- conventional pharmaceutical expedients such as sterilisation and can contain conventional pharmaceutical excipients such as preservatives, stabilizing agents, wetting agents, emulsifying agents, salts for the adjustment of osmotic pressure or buffers.
- the compositions can also contain other therapeutically active materials.
- a suitable pharmaceutical dosage unit can contain from about I to 5 mg daily of the aforesaid compounds and due to their long-lasting effect this dosage can be also administered in a single daily dose.
- the present invention furthermore relates to a process for the preparation of the new pyridazine derivatives of formula (I), comprising the reaction between a compound of the formula:
- reaction mass When heating is over, the reaction mass is taken up with a protic solvent, preferably aqueous or alcoholic, and the base of formula (I) is made free of alkalinization with suitable basic agents such as bicarbonates, carbonates, or alcoholates of alkali metals.
- a protic solvent preferably aqueous or alcoholic
- suitable basic agents such as bicarbonates, carbonates, or alcoholates of alkali metals.
- EXAMPLE 1 3-( Z-Carbethoxyhydrazino )-6-dimethylaminopyridazine hydrochloride
- a mixture of 1.57 g (0.01 moles) 3-chloro-6-dimethylaminopyridazine and 2.08 g (0.02 moles) monocarbethoxyhydrazine is warmed up for half an hour at 160C.
- the resulting mixture is cooled, water added thereto, the solid which separates filtered away and the filtrate neutralized with NaHCO, until a final pH 7.
- the mixture is then extracted with cloroform, the organic extract dried over sodium sulphate and the solvent evaporated.
- a flocky precipitate separates which is subsequently collected by filtration and crystallized from ethanol, to give with good yields 3-(Z-carbethoxyhydrazino)-6-[N- (Z-hydroxyethyl) methylaminol-pyridazine melting at l31-l33C.
- EXAMPLE 4 3-(Z-Carbethoxyhydrazino)-6-[di-(2-hydroxyethy1)- aminol-pyridazine hydrochloride
- a mixture of 4.34 g (0.02 moles) 3-chloro-6-bis-(2- hydroxyethyl)-aminopyridazine and 4.16 g (0.04 moles) monocarbethoxyhydrazine is warmed up to 140C and kept at such temperature for 1 hour. The mixture is cooled, methanol added thereto until solution, and neutralized with a methanol solution of sodium methoxide to pH 7.
- EXAMPLE 5 3 -(2-Carbethoxyhydrazino)-6-c1ial1ylaminopyridazine
- a mixture of 4.18 g (0.02 moles) 3-ch1oro-6-diallylaminopyridazine and 4.16 g (0.04 moles) monocarbethoxyhydrazine is warmed up to C and kept at this temperature for 1 hour.
- the mixture is taken up with cool water and sodium carbonate is added until neutral pH. it is then extracted with methylene chloride, the organic extracts collected together, dried over sodium sulphate and concentrated.
- the residual oil is purified by chromatography on silica gel column, eluting with a mixture of chloroform-methanol 9.5:0.5.
Abstract
6-SUBSTITUTED 3-CARBETHOXYHYDRAZINOPYRIDAZINES OF THE GENERAL FORMULA:
WHEREIN R1 and R2, which may be the same or different, represent a lower alkyl group containing from 1 to 6 carbon atoms, an allyl group, a 2-hydroxyethyl group or a 2-hydroxypropyl group, as well as the pharmaceutically acceptable salts thereof. Also a method of preparation. These compounds have anti-hypertensive activity.
WHEREIN R1 and R2, which may be the same or different, represent a lower alkyl group containing from 1 to 6 carbon atoms, an allyl group, a 2-hydroxyethyl group or a 2-hydroxypropyl group, as well as the pharmaceutically acceptable salts thereof. Also a method of preparation. These compounds have anti-hypertensive activity.
Description
United States Patent [1 1 Carpi et al.
[451 Dec. 9, 1975 6-SUBSTITUTED 3-CARBETHOXYHYDRAZINOPYRIDAZINE [75] Inventors: Carlo Carpi, Reggio Emilia; Luciano Dorigotti; Giorgio Pifferi, both of Milan, all of Italy [73] Assignee: l.S.F. S.p.A., Milan, Italy [22] Filed: Mar. 4, 1974 [21] Appl. No.1 447,523
[30] Foreign Application Priority Data Primary Examiner-Richard J. Gallagher Assistant Examiner-Anne Marie T. Tighe Attorney, Agent, or FirmStevens, Davis, Miller & Mosher ABSTRACT 6-substituted 3-carbethoxyhydrazinopyridazines of the general formula:
R O NI-INHCOOC2H5 wherein R and R which may be the same or different, represent a lower alkyl group containing from I to 6 carbon atoms, an ally! group, a 2hydroxyethyl group or a 2-hydroxypropyl group, as well as the pharmaceutically acceptable salts thereof. Also a method of preparation. These compounds have antihypertensive activity.
6 Claims, No Drawings 6-SUBSTITUTED 3-CARBETHOXYHYDRAZINOPYRIDAZINE The evaluation of the acute toxicity was carried out in the mouse administering the products by the intraperitoneal route at 6 different dosage levels. The approximate LD, was determined thereafter.
TABLE 'ED,.,= dose producing a 20% fall in pressure compared to the basal value.
The present invention relates to new derivatives of pyridazine possessing remarkable pharmacodynamic properties. More particularly, the invention relates to new o-substituted 3'carbethoxyhydrazinopyridazines of the general formula: V
- NHNH-COOC H or with organic acids, such as acetic, succinic, benzoic,
p-toluensulphonic acid etc.
It is known that some derivatives of 6-substituted 3- hydrazinopyridazine possess remarkable anti-hypertensive activity. However, the therapeutic applications of said drugs are limited by the fact that they cause tachy cardia, headache, vertigo, etc., owing to the rapidity with which the hypotensive effect develops. Furthermore, repeated daily administrations are necessary to maintain the desired effect.
It has now been discovered that in the class of derivatives of formula (I) where a Z-carbethoxyhydrazinic group is contained in the molecule, the anti-hypertensive effect develops with a slow progression and is definitely more prolonged compared to similar drugs such as Hydralazine and Binazin.
Some illustrative results obtained in the renal hypertensive awaken rat according to the method of A. Grollman (Proc. Soc. Exptl. Biol. Med., 57, 102,1944) are given in Table l. The products were administered orally'to groups of 4 rats for each dosage level. The ar terial pressure was measured by bloodless method immediately before and at the lst, 3rd, 5th, 7th, 12th, 24th, 36th, 48th and 60th hour after administration.
The results listed in the above Table show that the compounds of the present invention display low toxicity, high activity, and possess the characteristic of a more gradual development of the hypotensive effect, as proved by the value of maximum effect appearance times. The higher values of the half effect time show furthermore the really exceptional duration of the hypotensive effect developed in the experimentally hypertensive animal.
The compounds of the invention and pharmaceutically acceptable salts thereof are useful as pharmaceuticals and are characterized by activity as antihypertensive agents.
These compounds can be used in the form of conventional pharmaceutical preparations; for example, the aforesaid compounds can be mixed with conventional organic or inorganic, inert pharmaceutical carriers suitable for parenteral or enteral administration such as, for example, water, gelatin, lactose, starch, magnesium stearate, talc, vegetable oil, gums, polyalkylene glycols, vaseline or the like. They can be administered in conventional pharmaceutical forms, e.g. solid forms, for example, tablets, dragees, capsules and the like; or in liquid forms, for example, injectable solutions, suspensions or emulsions. Moreover, the pharmaceutical compositions containing compounds of this invention can be subjected to conventional pharmaceutical expedients such as sterilisation and can contain conventional pharmaceutical excipients such as preservatives, stabilizing agents, wetting agents, emulsifying agents, salts for the adjustment of osmotic pressure or buffers. The compositions can also contain other therapeutically active materials.
A suitable pharmaceutical dosage unit can contain from about I to 5 mg daily of the aforesaid compounds and due to their long-lasting effect this dosage can be also administered in a single daily dose.
The present invention furthermore relates to a process for the preparation of the new pyridazine derivatives of formula (I), comprising the reaction between a compound of the formula:
wherein R and R have the above meaning and X rep resents a chlorine or bromine atom and monocarbethoxyhydrazine:
H,N-NHCOOC,H, (111) Derivatives of formula (1]) used as starting materials are known, as is monocarbethoxyhydrazine (Ill). The compounds of formula (ll) are warmed up with two equivalents of monocarbethoxyhydrazine preferably in the absence of solvents and at a temperature ranging between 140l60C. The excess monocarbethoxyhydrazine serves to help the reaction, blocking the hydrochloric acid which forms during the condensation with the compounds of formula (11). The duration of the reaction is not critical but the operation is preferably car ried out during a short period of time ranging from about a half an hour to about 1 hour of heating. When heating is over, the reaction mass is taken up with a protic solvent, preferably aqueous or alcoholic, and the base of formula (I) is made free of alkalinization with suitable basic agents such as bicarbonates, carbonates, or alcoholates of alkali metals. The isolation of the final product is carried out by precipitation, concentration or extraction according to the usual methods, and successive purification can be carried out by conventional crystallization or chromatography.
The following Examples, which are not limitative, serve to illustrate the present invention.
EXAMPLE 1 3-( Z-Carbethoxyhydrazino )-6-dimethylaminopyridazine hydrochloride A mixture of 1.57 g (0.01 moles) 3-chloro-6-dimethylaminopyridazine and 2.08 g (0.02 moles) monocarbethoxyhydrazine is warmed up for half an hour at 160C. The resulting mixture is cooled, water added thereto, the solid which separates filtered away and the filtrate neutralized with NaHCO, until a final pH 7. The mixture is then extracted with cloroform, the organic extract dried over sodium sulphate and the solvent evaporated. The residual oil is purified by chromatography on silica gel, eluting with a mixture of chloroforimmethanol 8.5:1.5. The unitary fractions on thin layer chromatography with the same Rf are collected together, evaporated and the residue treated while warm with ethyl ether, and the residue filtered off. By addition of hydrogen chloride to the filtrate, 3-(2-carbethoxyhydrazino )-6-dimethylaminopyridazine hydrochloride precipitates with good yields melting at 2l52l7C (with dec). l.R. Spectrum (mineral oil, cm"): 3200 (NH), 1715 (C==O carbamate), 1595 (pyridazinic ring), 840 (two ortho-aromatic hydrogens).
Analysis: Calculated for C,H,,N,O,.HC1: C, 41.30; H, 6.16; N, 26.76; C1, 13.55. Found: C, 41.59; H, 6.20; N, 26.77, Cl, 13.29.
EXAMPLE 2 3-( Z-Carbethoxyhydrazino )-6-[ N-( Z-hydroxyethyl methylaminol-pyridazine A mixture of 1.87 g (0.01 moles) 3-ch1oro-6-[N-(2- hydroxyethyl)-methylaminol-pyridazine and 2.08 g (0.02 moles) monocarbethoxyhydrazine is warmed up to 155C and kept at this temperature for half an hour. The product is cooled and dissolved in water, alkalinized by addition of solid potassium carbonate and the aqueous solution saturated by adding sodium chloride.
A flocky precipitate separates which is subsequently collected by filtration and crystallized from ethanol, to give with good yields 3-(Z-carbethoxyhydrazino)-6-[N- (Z-hydroxyethyl) methylaminol-pyridazine melting at l31-l33C. 1.R. Spectrum (mineral oil, cm); 3320-3080 (OH and NH), 1715 (C=O carbamate), 1500 (pyridazinic ring), 840 (two ortho aromatic hydrogens).
Analysis: Calculated for C H N O C, 47.05; H, 6.71; N, 27.43. Found C, 46.89; H, 6.81; N, 27.74.
EXAMPLE 3 3-( 2-Carbethoxyhydrazino)-6-[N-(2-hydroxypropyl)- methylamino1-pyridazine A mixture of 6 g (0.029 moles) 3-chloro-6-[N-(2- hydroxypropyl)-methylamino]-pyridazine and 6.2 g (0.069 moles) monocarbethoxyhydrazine is warmed up to 145C and kept at this temperature for 1 hour. After cooling, the residue is taken up in water and the solution extracted with chloroform. The aqueous phase is cooled and treated with potassicurn carbonate until complete precipitation. The precipitation is collected and purified by crystallization from ethanol to give with good yields 3-(2-carbethoxyhydrazino)-6-[N-(2- hydroxypropyl)-methy1amino]-pyridazine melting at 150-152C.
Analysis: Calculated for C H,,N,O,: C, 49.06; H, 7.11; N, 26.00. Found C, 49.15; H, 7.50; N, 26.04.
EXAMPLE 4 3-(Z-Carbethoxyhydrazino)-6-[di-(2-hydroxyethy1)- aminol-pyridazine hydrochloride A mixture of 4.34 g (0.02 moles) 3-chloro-6-bis-(2- hydroxyethyl)-aminopyridazine and 4.16 g (0.04 moles) monocarbethoxyhydrazine is warmed up to 140C and kept at such temperature for 1 hour. The mixture is cooled, methanol added thereto until solution, and neutralized with a methanol solution of sodium methoxide to pH 7. The solvent is evaporated and the residual oil purified by chromatography on silica gel column, eluting with a mixture of chloroformzmethanol :15. The unitary fractions on thin layer chromatography with the same Rf are collected together, evaporated and the residue, taken up with acetone, is acidified with hydrogen chloride. Good yields of 3-(2- carbethoxyhydrazino)-6-[di-(2-hydroxyethyl)-amino]- pyridazine hydrochloride melting at 162-l65C (with dec.) are obtained.
l.R. Spectrum (mineral oil, cm): 3450-3200 (OH and NH), 1710 (C=O carbamate) 1595 (pyridazinic ring). 840 (two ortho aromatic hydrogens).
Calculated for C,,H,,N,O .HCI: C, 41.06; H, 6.26; CI, 11.01; N, 21.76. Found C, 40.90; H, 5.90; Cl, 10.50; N, 22.41.
EXAMPLE 5 3 -(2-Carbethoxyhydrazino)-6-c1ial1ylaminopyridazine A mixture of 4.18 g (0.02 moles) 3-ch1oro-6-diallylaminopyridazine and 4.16 g (0.04 moles) monocarbethoxyhydrazine is warmed up to C and kept at this temperature for 1 hour. The mixture is taken up with cool water and sodium carbonate is added until neutral pH. it is then extracted with methylene chloride, the organic extracts collected together, dried over sodium sulphate and concentrated. The residual oil is purified by chromatography on silica gel column, eluting with a mixture of chloroform-methanol 9.5:0.5. The unitary fractions on thin layer chromatography with the same Rf are collected together; the solvent is eliminated by evaporation and a yellow oil formed by 3-( 2- carbethoxyhydrazino)-6-diallylaminopyridazine is obtained.
[.R. Spectrum (mineral oil, cm); 3350-3100 (NH), 1715 (C=O carbamate), 1645 (Cl-[=CH,), 830-825 (two ortho aromatic hydrogens).
Analysis: Calculated for c, H,,N 0,: C, 56.30; H, 6.90; N, 25.25. Found C, 56.01; H, 6.80; N, 25.48.
What is claimed is:
l. A compound of the formula:
m NHNH-COOC2H5 V (1) 2
Claims (6)
1. A COMPOUND OF THE FORMULA:
2. 3-(2-Carbethoxyhydrazino)-6-dimethylaminopyridazine and its pharmaceutically acceptable salts.
3. 3-(2-Carbethoxyhydrazino)-6-(N-(2-hydroxyethyl)methyl-amino)-pyridazine and its pharmaceutically acceptable salts.
4. 3-(2-Carbethoxyhydrazino)-6-(N-(2-hydroxypropyl)methyl-amino)-pyridazine and its pharmaceutically acceptable salts.
5. 3-(2-Carbethoxyhydrazino)-6-(di-(2-hydroxyethyl)-amino)-pyridazine and its pharmaceutically acceptable salts.
6. 3-(2-Carbethoxyhydrazino)-6-diallylaminopyridazine and its pharmaceutically acceptable salts.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/613,865 US4002753A (en) | 1973-03-07 | 1975-09-16 | 6-Substituted 3-carbethoxyhydrazinopyridazines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2129773 | 1973-03-07 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US05/613,865 Continuation-In-Part US4002753A (en) | 1973-03-07 | 1975-09-16 | 6-Substituted 3-carbethoxyhydrazinopyridazines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3925381A true US3925381A (en) | 1975-12-09 |
Family
ID=11179697
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US447523A Expired - Lifetime US3925381A (en) | 1973-03-07 | 1974-03-04 | 6-Substituted 3-carbethoxyhydrazinopyridazine |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US3925381A (en) |
| JP (1) | JPS5229751B2 (en) |
| AR (1) | AR197762A1 (en) |
| AT (1) | AT330194B (en) |
| AU (1) | AU474997B2 (en) |
| BE (1) | BE811847A (en) |
| CA (1) | CA1016549A (en) |
| CH (1) | CH586683A5 (en) |
| DE (1) | DE2410201C3 (en) |
| DK (1) | DK135504B (en) |
| ES (1) | ES423950A1 (en) |
| FI (1) | FI57589C (en) |
| FR (1) | FR2220264B1 (en) |
| GB (1) | GB1407581A (en) |
| IE (1) | IE40847B1 (en) |
| IL (1) | IL44341A (en) |
| NL (1) | NL165156C (en) |
| NO (1) | NO140010C (en) |
| PH (2) | PH10333A (en) |
| SE (1) | SE403107B (en) |
| YU (2) | YU57374A (en) |
| ZA (1) | ZA741396B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4002753A (en) * | 1973-03-07 | 1977-01-11 | I.S.F. S.P.A. | 6-Substituted 3-carbethoxyhydrazinopyridazines |
| US4086343A (en) * | 1976-06-11 | 1978-04-25 | I.S.F. Spa | Acylated hydrazinopyridazine antihypertensives |
| US4092311A (en) * | 1976-06-03 | 1978-05-30 | American Cyanamid Company | Hypotensive alkyl-3-[6-(aryl)-3-pyridazinyl]-carbazates |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE30911T1 (en) * | 1982-06-23 | 1987-12-15 | Teikoku Hormone Mfg Co Ltd | HYDRAZINOPYRIDAZINE COMPOUND, PROCESS FOR ITS PREPARATION AND ITS USE AS A MEDICINAL PRODUCT. |
| IT1164198B (en) * | 1983-04-28 | 1987-04-08 | Isf Spa | PREPARATION OF A PHARMACOLOGICALLY ACTIVE PYRIDAZINIC DERIVATIVE |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3535317A (en) * | 1965-10-08 | 1970-10-20 | Lepetit Spa | 3-hydrazinopyridazines having hypotensive activity |
| US3706744A (en) * | 1970-11-16 | 1972-12-19 | Sandoz Ag | Hydrazone derivatives of 3-substituted amino-6-hydrazino pyridazines |
| US3769278A (en) * | 1970-12-15 | 1973-10-30 | Isf Spa | Antihypertensive 6-substituted 3-hydrazino-pyridazines and their preparation |
-
1974
- 1974-03-04 CA CA193,915A patent/CA1016549A/en not_active Expired
- 1974-03-04 BE BE141624A patent/BE811847A/en not_active IP Right Cessation
- 1974-03-04 SE SE7402859A patent/SE403107B/en not_active IP Right Cessation
- 1974-03-04 DE DE2410201A patent/DE2410201C3/en not_active Expired
- 1974-03-04 IL IL44341A patent/IL44341A/en unknown
- 1974-03-04 AR AR252608A patent/AR197762A1/en active
- 1974-03-04 GB GB961974A patent/GB1407581A/en not_active Expired
- 1974-03-04 CH CH301774A patent/CH586683A5/xx not_active IP Right Cessation
- 1974-03-04 FI FI627/74A patent/FI57589C/en active
- 1974-03-04 ZA ZA00741396A patent/ZA741396B/en unknown
- 1974-03-04 AT AT175174A patent/AT330194B/en not_active IP Right Cessation
- 1974-03-04 IE IE454/74A patent/IE40847B1/en unknown
- 1974-03-04 US US447523A patent/US3925381A/en not_active Expired - Lifetime
- 1974-03-05 PH PH15575*A patent/PH10333A/en unknown
- 1974-03-05 YU YU00573/74A patent/YU57374A/en unknown
- 1974-03-05 YU YU573/74A patent/YU35877B/en unknown
- 1974-03-06 DK DK121574AA patent/DK135504B/en not_active IP Right Cessation
- 1974-03-06 NL NL7403050.A patent/NL165156C/en not_active IP Right Cessation
- 1974-03-06 ES ES423950A patent/ES423950A1/en not_active Expired
- 1974-03-06 FR FR7407564A patent/FR2220264B1/fr not_active Expired
- 1974-03-06 NO NO740779A patent/NO140010C/en unknown
- 1974-03-06 JP JP49025336A patent/JPS5229751B2/ja not_active Expired
- 1974-03-06 AU AU66331/74A patent/AU474997B2/en not_active Expired
-
1976
- 1976-09-01 PH PH18857A patent/PH10949A/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3535317A (en) * | 1965-10-08 | 1970-10-20 | Lepetit Spa | 3-hydrazinopyridazines having hypotensive activity |
| US3706744A (en) * | 1970-11-16 | 1972-12-19 | Sandoz Ag | Hydrazone derivatives of 3-substituted amino-6-hydrazino pyridazines |
| US3769278A (en) * | 1970-12-15 | 1973-10-30 | Isf Spa | Antihypertensive 6-substituted 3-hydrazino-pyridazines and their preparation |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4002753A (en) * | 1973-03-07 | 1977-01-11 | I.S.F. S.P.A. | 6-Substituted 3-carbethoxyhydrazinopyridazines |
| US4092311A (en) * | 1976-06-03 | 1978-05-30 | American Cyanamid Company | Hypotensive alkyl-3-[6-(aryl)-3-pyridazinyl]-carbazates |
| US4086343A (en) * | 1976-06-11 | 1978-04-25 | I.S.F. Spa | Acylated hydrazinopyridazine antihypertensives |
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